Guazuma ulmifolia Lam. (Malvaceae) reduz estresse oxidativo em células sanguíneas e previne cardiotoxidade induzida por doxorrubicina

Abstract

Oxidative stress has a key role in several diseases, as well as doxorubicin-induced cardiotoxicity (DOX) during chemotherapy, which limits the clinical application of this drug. However, the combination of DOX and antioxidants has reduced this toxicity. In this study, we evaluated the antioxidant capacity of Guazuma ulmifolia stem bark (GUEsb) and Guazuma ulmifolia leaves (GUEl) extracts in blood cells submitted to different oxidizing agents. In addition, we investigated the effects of GUEsb on acute toxicity and on the prevention of DOX-induced cardiotoxicity in vivo. For this, we evaluated the direct antioxidant activity by capturing the DPPH free radical, inhibiting lipid peroxidation induced by AAPH or DOX in human erythrocytes and quantifying intracellular EROs by fluorescence probe DCFH-DA in K562 erythroleukemic cells stimulated with hydrogen peroxide. The viability of K562 erythroleukemic cells and leukocytes treated with GUEsb was also evaluated by the MTT method in the absence or presence of DOX. In addition, the acute toxicity and cardioprotective effect of GUEsb in C57B1/6 mice treated with DOX were evaluated. The GUEsb and GUEl showed antioxidant activities by eliminating free radicals, anti-hemolytic action and reducing of the malondialdehyde (MDA) content generated in human erythrocytes stimulated by oxidizing agents. When presenting better overall antioxidant activity, GUEsb was selected for the other studies. GUEsb showed reduction of intracellular ROS in K562 cells stimulated by hydrogen peroxide, did not interfere in the cytotoxicity of DOX in K562 cells and did not induce leukocyte cell death but protected them against DOX-induced death, did not present acute toxicity in vivo and was able to prevent the generation of MDA in the cardiac tissue of mice treated with DOX, demonstrating its cardioprotective action. Together, the results show that GUEsb and GUEl are natural antioxidants and therefore possible alternatives for the treatment of diseases associated with oxidative stress and, in particular, GUEsb may play an adjuvant role in DOX chemotherapy.